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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:CLIP4-BRE

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CLIP4-BRE
FusionPDB ID: 17186
FusionGDB2.0 ID: 17186
HgeneTgene
Gene symbol

CLIP4

BRE

Gene ID

79745

9577

Gene nameCAP-Gly domain containing linker protein family member 4BRISC and BRCA1 A complex member 2
SynonymsRSNL2BRCC4|BRCC45|BRE
Cytomap

2p23.2

2p23.2

Type of geneprotein-codingprotein-coding
DescriptionCAP-Gly domain-containing linker protein 4CAP-GLY domain containing linker protein family, member 4restin-like protein 2BRISC and BRCA1-A complex member 2BRCA1-A complex subunit BREBRCA1/BRCA2-containing complex subunit 45BRCA1/BRCA2-containing complex, subunit 4brain and reproductive organ-expressed (TNFRSF1A modulator)brain and reproductive organ-expressed protein
Modification date2020031320200313
UniProtAcc

Q8N3C7

Main function of 5'-partner protein:
.
Ensembl transtripts involved in fusion geneENST idsENST00000320081, ENST00000401605, 
ENST00000404424, ENST00000401617, 
ENST00000481628, 
ENST00000603461, 
ENST00000342045, ENST00000344773, 
ENST00000361704, ENST00000379624, 
ENST00000379632, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 5 X 5=15020 X 20 X 12=4800
# samples 630
** MAII scorelog2(6/150*10)=-1.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(30/4800*10)=-4
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CLIP4 [Title/Abstract] AND BRE [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CLIP4 [Title/Abstract] AND BRE [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CLIP4(29344387)-BRE(28521205), # samples:2
Anticipated loss of major functional domain due to fusion event.CLIP4-BRE seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
CLIP4-BRE seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
TgeneBRE

GO:0043066

negative regulation of apoptotic process

15465831



check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr2:29344387/chr2:28521205)
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
- How to search
1. Put your fusion gene symbol.
2. Press the tab key until there will be shown the breakpoint information filled.
4. Go down and press 'Search' tab twice.
4. Go down to have the hyperlink of the search result.
5. Click the hyperlink.
6. See the FGviewer result for your fusion gene.
FGviewer

check buttonRetention analysis results of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features, are available here.

check buttonFusion gene breakpoints across CLIP4 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across BRE (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000401605CLIP4chr229344387+ENST00000344773BREchr228521205+1171391307798163
ENST00000401605CLIP4chr229344387+ENST00000379624BREchr228521205+997391258608116
ENST00000401605CLIP4chr229344387+ENST00000342045BREchr228521205+997391258608116
ENST00000401605CLIP4chr229344387+ENST00000379632BREchr228521205+1069391307696129
ENST00000401605CLIP4chr229344387+ENST00000361704BREchr228521205+1069391307696129
ENST00000404424CLIP4chr229344387+ENST00000344773BREchr228521205+1245465381872163
ENST00000404424CLIP4chr229344387+ENST00000379624BREchr228521205+1071465332682116
ENST00000404424CLIP4chr229344387+ENST00000342045BREchr228521205+1071465332682116
ENST00000404424CLIP4chr229344387+ENST00000379632BREchr228521205+1143465381770129
ENST00000404424CLIP4chr229344387+ENST00000361704BREchr228521205+1143465381770129
ENST00000320081CLIP4chr229344387+ENST00000344773BREchr228521205+1168388304795163
ENST00000320081CLIP4chr229344387+ENST00000379624BREchr228521205+994388255605116
ENST00000320081CLIP4chr229344387+ENST00000342045BREchr228521205+994388255605116
ENST00000320081CLIP4chr229344387+ENST00000379632BREchr228521205+1066388304693129
ENST00000320081CLIP4chr229344387+ENST00000361704BREchr228521205+1066388304693129

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000401605ENST00000344773CLIP4chr229344387+BREchr228521205+0.52050590.4794941
ENST00000401605ENST00000379624CLIP4chr229344387+BREchr228521205+0.0419392030.9580608
ENST00000401605ENST00000342045CLIP4chr229344387+BREchr228521205+0.0419392030.9580608
ENST00000401605ENST00000379632CLIP4chr229344387+BREchr228521205+0.0380713120.9619287
ENST00000401605ENST00000361704CLIP4chr229344387+BREchr228521205+0.0380713120.9619287
ENST00000404424ENST00000344773CLIP4chr229344387+BREchr228521205+0.35316510.6468349
ENST00000404424ENST00000379624CLIP4chr229344387+BREchr228521205+0.0433184280.9566816
ENST00000404424ENST00000342045CLIP4chr229344387+BREchr228521205+0.0433184280.9566816
ENST00000404424ENST00000379632CLIP4chr229344387+BREchr228521205+0.04944610.95055395
ENST00000404424ENST00000361704CLIP4chr229344387+BREchr228521205+0.04944610.95055395
ENST00000320081ENST00000344773CLIP4chr229344387+BREchr228521205+0.688234270.31176573
ENST00000320081ENST00000379624CLIP4chr229344387+BREchr228521205+0.091780850.90821916
ENST00000320081ENST00000342045CLIP4chr229344387+BREchr228521205+0.091780850.90821916
ENST00000320081ENST00000379632CLIP4chr229344387+BREchr228521205+0.072157860.92784214
ENST00000320081ENST00000361704CLIP4chr229344387+BREchr228521205+0.072157860.92784214

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for CLIP4-BRE

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CLIP4chr229344387BREchr22852120538828SFPFLQHQCLQTVLTCLCFSLETSQL
CLIP4chr229344387BREchr22852120538844IFSISAAPMPSDCVDLPLFFPRDQPT
CLIP4chr229344387BREchr22852120539128SFPFLQHQCLQTVLTCLCFSLETSQL
CLIP4chr229344387BREchr22852120539144IFSISAAPMPSDCVDLPLFFPRDQPT
CLIP4chr229344387BREchr22852120546528SFPFLQHQCLQTVLTCLCFSLETSQL
CLIP4chr229344387BREchr22852120546544IFSISAAPMPSDCVDLPLFFPRDQPT

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Potential FusionNeoAntigen Information of CLIP4-BRE in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
CLIP4-BRE_29344387_28521205.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
CLIP4-BREchr229344387chr228521205388HLA-B48:01HQCLQTVL0.99210.5745614
CLIP4-BREchr229344387chr228521205388HLA-B35:03MPSDCVDL0.92230.9264816
CLIP4-BREchr229344387chr228521205388HLA-B39:01QHQCLQTVL0.99910.9523514
CLIP4-BREchr229344387chr228521205388HLA-B38:02QHQCLQTVL0.99870.9821514
CLIP4-BREchr229344387chr228521205388HLA-B39:24QHQCLQTVL0.99870.5603514
CLIP4-BREchr229344387chr228521205388HLA-B38:01QHQCLQTVL0.99840.9822514
CLIP4-BREchr229344387chr228521205388HLA-B39:06QHQCLQTVL0.99730.8734514
CLIP4-BREchr229344387chr228521205388HLA-B14:02QHQCLQTVL0.98740.8891514
CLIP4-BREchr229344387chr228521205388HLA-B14:01QHQCLQTVL0.98740.8891514
CLIP4-BREchr229344387chr228521205388HLA-B15:18QHQCLQTVL0.88040.718514
CLIP4-BREchr229344387chr228521205388HLA-B35:03MPSDCVDLPL0.98980.9103818
CLIP4-BREchr229344387chr228521205388HLA-B35:08MPSDCVDLPL0.98620.9335818
CLIP4-BREchr229344387chr228521205388HLA-B48:01LQHQCLQTVL0.9740.772414
CLIP4-BREchr229344387chr228521205388HLA-B35:04MPSDCVDLPL0.97250.9674818
CLIP4-BREchr229344387chr228521205388HLA-B35:02MPSDCVDLPL0.97250.9674818
CLIP4-BREchr229344387chr228521205388HLA-B35:03APMPSDCVDL0.80940.9056616
CLIP4-BREchr229344387chr228521205388HLA-B35:02APMPSDCVDL0.6340.961616
CLIP4-BREchr229344387chr228521205388HLA-B35:04APMPSDCVDL0.6340.961616
CLIP4-BREchr229344387chr228521205388HLA-B82:01APMPSDCVDL0.42740.5223616
CLIP4-BREchr229344387chr228521205388HLA-B35:01MPSDCVDLPLF0.99910.9334819
CLIP4-BREchr229344387chr228521205388HLA-B35:08MPSDCVDLPLF0.99890.9499819
CLIP4-BREchr229344387chr228521205388HLA-B35:05MPSDCVDLPLF0.99850.6486819
CLIP4-BREchr229344387chr228521205388HLA-B35:03MPSDCVDLPLF0.99540.9204819
CLIP4-BREchr229344387chr228521205388HLA-B39:09QHQCLQTVL0.99920.7384514
CLIP4-BREchr229344387chr228521205388HLA-B39:12QHQCLQTVL0.9990.9561514
CLIP4-BREchr229344387chr228521205388HLA-B39:05QHQCLQTVL0.99840.9495514
CLIP4-BREchr229344387chr228521205388HLA-B14:03QHQCLQTVL0.56080.8262514
CLIP4-BREchr229344387chr228521205388HLA-C01:17AAPMPSDCV0.03280.9741514
CLIP4-BREchr229344387chr228521205388HLA-B07:12APMPSDCVDL0.9750.5814616
CLIP4-BREchr229344387chr228521205388HLA-B35:12MPSDCVDLPL0.97250.9674818
CLIP4-BREchr229344387chr228521205388HLA-B39:10MPSDCVDLPL0.94480.9417818
CLIP4-BREchr229344387chr228521205388HLA-B39:10APMPSDCVDL0.7450.9313616
CLIP4-BREchr229344387chr228521205388HLA-B35:12APMPSDCVDL0.6340.961616
CLIP4-BREchr229344387chr228521205388HLA-B42:01APMPSDCVDL0.55170.8408616
CLIP4-BREchr229344387chr228521205388HLA-B39:31QHQCLQTVL0.99920.9524514
CLIP4-BREchr229344387chr228521205388HLA-B38:05QHQCLQTVL0.99840.9822514
CLIP4-BREchr229344387chr228521205388HLA-B15:09QHQCLQTVL0.99410.8147514
CLIP4-BREchr229344387chr228521205388HLA-B39:11QHQCLQTVL0.89520.934514
CLIP4-BREchr229344387chr228521205388HLA-C01:03AAPMPSDCV0.05550.9736514
CLIP4-BREchr229344387chr228521205388HLA-C01:02AAPMPSDCV0.050.9742514
CLIP4-BREchr229344387chr228521205388HLA-B15:73LQHQCLQTVL0.99610.9724414
CLIP4-BREchr229344387chr228521205388HLA-B15:30LQHQCLQTVL0.99320.9732414
CLIP4-BREchr229344387chr228521205388HLA-B35:13MPSDCVDLPL0.98770.9133818
CLIP4-BREchr229344387chr228521205388HLA-B35:09MPSDCVDLPL0.97250.9674818
CLIP4-BREchr229344387chr228521205388HLA-B67:01MPSDCVDLPL0.94740.8796818
CLIP4-BREchr229344387chr228521205388HLA-B35:13APMPSDCVDL0.76660.9095616
CLIP4-BREchr229344387chr228521205388HLA-B67:01APMPSDCVDL0.73520.8523616
CLIP4-BREchr229344387chr228521205388HLA-B35:09APMPSDCVDL0.6340.961616
CLIP4-BREchr229344387chr228521205388HLA-B82:02APMPSDCVDL0.42740.5223616
CLIP4-BREchr229344387chr228521205388HLA-B35:77MPSDCVDLPLF0.99910.9334819
CLIP4-BREchr229344387chr228521205388HLA-B35:23MPSDCVDLPLF0.9990.9336819
CLIP4-BREchr229344387chr228521205388HLA-B35:17MPSDCVDLPLF0.99860.851819
CLIP4-BREchr229344387chr228521205388HLA-B35:30MPSDCVDLPLF0.99860.851819
CLIP4-BREchr229344387chr228521205388HLA-B35:24MPSDCVDLPLF0.98250.9191819

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Potential FusionNeoAntigen Information of CLIP4-BRE in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of CLIP4-BRE

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
491APMPSDCVDLPLFFCLIP4BREchr229344387chr228521205388
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
3465HQCLQTVLTCLCFSCLIP4BREchr229344387chr228521205388

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CLIP4-BRE

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN491APMPSDCVDLPLFF-7.9962-8.1096
HLA-B14:023BVN491APMPSDCVDLPLFF-5.70842-6.74372
HLA-B52:013W39491APMPSDCVDLPLFF-6.83737-6.95077
HLA-B52:013W39491APMPSDCVDLPLFF-4.4836-5.5189
HLA-A11:014UQ2491APMPSDCVDLPLFF-10.0067-10.1201
HLA-A11:014UQ2491APMPSDCVDLPLFF-9.03915-10.0745
HLA-A24:025HGA491APMPSDCVDLPLFF-6.56204-6.67544
HLA-A24:025HGA491APMPSDCVDLPLFF-5.42271-6.45801
HLA-B44:053DX8491APMPSDCVDLPLFF-7.85648-8.89178
HLA-B44:053DX8491APMPSDCVDLPLFF-5.3978-5.5112
HLA-A02:016TDR491APMPSDCVDLPLFF-3.37154-4.40684
HLA-B14:023BVN3465HQCLQTVLTCLCFS-7.9962-8.1096
HLA-B14:023BVN3465HQCLQTVLTCLCFS-5.70842-6.74372
HLA-B52:013W393465HQCLQTVLTCLCFS-6.83737-6.95077
HLA-B52:013W393465HQCLQTVLTCLCFS-4.4836-5.5189
HLA-A11:014UQ23465HQCLQTVLTCLCFS-10.0067-10.1201
HLA-A11:014UQ23465HQCLQTVLTCLCFS-9.03915-10.0745
HLA-A24:025HGA3465HQCLQTVLTCLCFS-6.56204-6.67544
HLA-A24:025HGA3465HQCLQTVLTCLCFS-5.42271-6.45801
HLA-B44:053DX83465HQCLQTVLTCLCFS-7.85648-8.89178
HLA-B44:053DX83465HQCLQTVLTCLCFS-5.3978-5.5112
HLA-A02:016TDR3465HQCLQTVLTCLCFS-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of CLIP4-BRE

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
CLIP4-BREchr229344387chr228521205414LQHQCLQTVLCTGCAGCACCAATGCCTTCAGACTGTGTTG
CLIP4-BREchr229344387chr228521205514AAPMPSDCVCAGCACCAATGCCTTCAGACTGTGTTG
CLIP4-BREchr229344387chr228521205514QHQCLQTVLCAGCACCAATGCCTTCAGACTGTGTTG
CLIP4-BREchr229344387chr228521205614HQCLQTVLCACCAATGCCTTCAGACTGTGTTG
CLIP4-BREchr229344387chr228521205616APMPSDCVDLCACCAATGCCTTCAGACTGTGTTGACCTGC
CLIP4-BREchr229344387chr228521205816MPSDCVDLTGCCTTCAGACTGTGTTGACCTGC
CLIP4-BREchr229344387chr228521205818MPSDCVDLPLTGCCTTCAGACTGTGTTGACCTGCCTCTGT
CLIP4-BREchr229344387chr228521205819MPSDCVDLPLFTGCCTTCAGACTGTGTTGACCTGCCTCTGTTTT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of CLIP4-BRE

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
OVCLIP4-BREchr229344387ENST00000320081chr228521205ENST00000342045TCGA-25-1323-01A
OVCLIP4-BREchr229344387ENST00000320081chr228521205ENST00000344773TCGA-25-1323-01A

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Potential target of CAR-T therapy development for CLIP4-BRE

check button Predicted 3D structure. We used RoseTTAFold.

check buttonRetention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to CLIP4-BRE

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to CLIP4-BRE

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource